TY - JOUR
T1 - Triiodo-L-thyronine rapidly stimulates alveolar fluid clearance in normal and hyperoxia-injured lungs
AU - Bhargava, Maneesh
AU - Runyon, Marie R.
AU - Smirnov, Dmitri
AU - Lei, Jianxun
AU - Groppoli, Thomas J.
AU - Mariash, Cary N.
AU - Wangensteen, Douglas
AU - Ingbar, David H
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/9/1
Y1 - 2008/9/1
N2 - Rationale: Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na,K-ATPase and other ion transport proteins. Objectives: In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3′,5 triiodo-L-thyronine (T 3). Methods: AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time. Measurements and Main Results: Systemic treatment with intraperitoneal injections of T3 for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T3-treated rats had higher Na,K-ATPase hydrolytic activity. T3 (10-6M), but not reverse T3 (3,3′,5′ triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T3 in ex vivo isolated lungs, suggesting a direct effect of T3 on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T3 rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury. Conclusions: Airspace T3 rapidly stimulates AFC by direct effects on the alveolar epithelium in rat lungs with and without lung injury.
AB - Rationale: Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na,K-ATPase and other ion transport proteins. Objectives: In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3′,5 triiodo-L-thyronine (T 3). Methods: AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time. Measurements and Main Results: Systemic treatment with intraperitoneal injections of T3 for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T3-treated rats had higher Na,K-ATPase hydrolytic activity. T3 (10-6M), but not reverse T3 (3,3′,5′ triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T3 in ex vivo isolated lungs, suggesting a direct effect of T3 on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T3 rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury. Conclusions: Airspace T3 rapidly stimulates AFC by direct effects on the alveolar epithelium in rat lungs with and without lung injury.
KW - Acute respiratory distress syndrome
KW - Alveolar Na,K-ATPase
KW - Alveolar fluid clearance
KW - Thyroid hormone
KW - Type 2 cell
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U2 - 10.1164/rccm.200709-1429OC
DO - 10.1164/rccm.200709-1429OC
M3 - Article
C2 - 18556623
AN - SCOPUS:51349157222
VL - 178
SP - 506
EP - 512
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 5
ER -